The principal goal of this investigation is to determine the mechanisms of short-term and long-term control of the set of liver enzymes that catalyze the formation of long-chain fatty acids. Although whole animal experiments are contemplated, the principal experimental approach employs maintenance cultures of liver parenchymal cells (hepatocytes) that have been separated from whole liver by perfusion with collagenase. The response of these cells to added insulin and glucagon is evaluated in terms of the rate of incorporation of tritiated water (3H2O) or 14C-labelled acetate into fatty acids. Key lipogenic enzyme activity is also determined in the hepatocyte cytosol. A delineation of preinduction events is the focus of present research. These include: change in concentration and flux of key lipogenic precursors as a function of time following the insulin signal; and change in concentration of the inactive (phosphorylated) and active (dephosphorylated) forms of acetyl CoA carboxylase and other enzymes as a function of preinduction time. Special attention is directed toward protein phosphatases and their protein inhibitors.